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Differential Activation of Unconventional T Cells, Including iNKT Cells, in Alcohol‐Related Liver Disease
- Source :
- Alcohol Clin Exp Res
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- BACKGROUND: Liver is enriched in several innate-like unconventional T cells but their role in alcohol-related liver disease (ALD) is not fully understood. Studies in several acute alcohol feeding models but not in chronic alcoholic steatohepatitis (ASH) model have shown that invariant natural killer T (iNKT) cells play a pathogenic role in ALD. Here, we investigated the activation of iNKT cells in an intragastric (iG) infusion model of chronic ASH as well as the frequency and cytokine phenotype of three different unconventional T cells: iNKT, mucosal-associated invariant T (MAIT) and CD8(+)CD161(hi)Vα7.2(−) cells in peripheral blood of ALD patients. METHODS: Hepatic iNKT cells were investigated using the iG model of chronic ASH that combine feeding of High-Cholesterol/High-Fat diet (HCFD) with intragastric feeding of ethanol diet (HCFD+iG Alc). Human iNKT, MAIT and CD8(+)CD161(hi)Vα7.2(−) cells were examined by flow cytometry in peripheral blood of patients with severe alcoholic hepatitis (SAH) and chronic alcoholics (ChA) and compared with healthy controls. RESULTS: In the iG model of chronic ASH, IFNγ(+) iNKT cells accumulate in their livers compared with pair-fed control mice and activated hepatic iNKT cells show high expression of Fas and FasL. Notably, IFNγ(+) iNKT cells are also significantly increased in peripheral blood of ChA patients compared with SAH patients. MAIT cells are significantly reduced in all ALD patients, but CD8(+)CD161(hi)Vα7.2(−) cells are increased in SAH patients. Although, MAIT and CD8(+)CD161(hi)Vα7.2(−) cells displayed a similar cytokine production profile, IFNγ and TNFα production is significantly increased in SAH patients while significant IL-17A production is found in ChA patients. CONCLUSIONS: We found that the three unconventional T cells are activated in ALD patients showing interesting differences in their frequency and cytokine production profile between SAH and ChA patients. In the iG murine model of chronic ASH, iNKT cells are also activated secreting pro-inflammatory cytokines suggesting their involvement in liver disease.
- Subjects :
- Male
T-Lymphocytes
medicine.medical_treatment
030508 substance abuse
Medicine (miscellaneous)
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Toxicology
Mucosal-Associated Invariant T Cells
Article
Fas ligand
Cell Line
Proinflammatory cytokine
Flow cytometry
Mice
03 medical and health sciences
Liver disease
0302 clinical medicine
medicine
Animals
Humans
Lymphocyte Count
Liver Diseases, Alcoholic
Ethanol
medicine.diagnostic_test
Hepatitis, Alcoholic
Chemistry
Middle Aged
medicine.disease
Mice, Inbred C57BL
Alcoholism
Psychiatry and Mental health
Cytokine
Liver
Immunology
Cytokines
Natural Killer T-Cells
Tumor necrosis factor alpha
Steatohepatitis
0305 other medical science
030217 neurology & neurosurgery
CD8
NK Cell Lectin-Like Receptor Subfamily B
Subjects
Details
- ISSN :
- 15300277 and 01456008
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- Alcoholism: Clinical and Experimental Research
- Accession number :
- edsair.doi.dedup.....21fc0dfa02e80e63f41e7249e37ff07e
- Full Text :
- https://doi.org/10.1111/acer.14323